Supplementary Table 3.

Indirect Evidence of Proposed COVID-19 Therapies

Medication class	Medication	Sourcea	Indirect	GI adverse events					Other
				Nausea/vomiting	Abdominal pain	Diarrhea	Jaundice	Hepatotoxicity
Antiviral	Lopinavir/ritonavir	FDA/ manufacturer's label110	HIV	Nausea (5%–16%); vomiting (children 21%; adults 2%–7%)	Reported 1%–11%	7%–28%; greater with once-daily dosing	—	Increased serum ALT: 1%–11%; hepatitis including AST/ALT/GGT elevations: 4%; hyperbilirubinemia (children 3%; adults 1%)	Dysgeusia (children 22%; adults <2%); hyperamylasemia (3%–8%), dyspepsia (<6%), increased lipase (3%–5%), flatulence (1-4%), gastroenteritis (3%)
		NIH Liver Tox111	HIV					Range from mild to ALF. Recovery takes 1–2 mo. Do not re-challenge with medication. Monitor for exacerbation of HBV/HCV
		Momattin,105 2019	MERS	Prevalence of GI AEs not reported in this SR
		Yao,106 2020	SARS/MERS	AEs not reported in this SR (can check primary studies)					SARS: 2 retrospective cohort studies (combined with steroids); MERS: 1 RCT combined with IFN, 1 retrospective cohort combined with IFN/ribavirin, and 2 case reports also combined with IFN/ribavirin
	Remdesivir	Al-Tawfiq,107 2020	MERS
		Sheahan,108 2020	MERS
Antimalarial	Chloroquine	FDA/ manufacturer's label/NIH Liver Tox111,112	Malaria	Reported; frequency not defined	Abdominal cramps reported; frequency not defined	Reported; frequency not defined		Rarely linked to aminotransferase elevations or clinically apparent liver injury. In patients with AIP or PCT, it can trigger an attack with fever and serum aminotransferase elevations, sometimes resulting in jaundice	Minor metabolism by liver (∼30%); mostly excreted in urine	Likelihood score: D (possible rare cause of clinically apparent liver injury)
	Hydroxychloroquine113	FDA / Manufacturer's label	Malaria / SLE	Reported; frequency not defined	Reported; frequency not defined	Reported; frequency not defined		Same as chloroquine above; can be exchanged with chloroquine as most reactions are hypersensitivity and no known cross reactivity to hepatic injury		Likelihood score: D (possible rare cause of clinically apparent liver injury)

AE, adverse event; AIP, acute intermittent porphyria; ALF, acute liver failure; GGT, gamma-glutamyl transferase; HBV, hepatitis B virus; HCV, hepatitis C virus; IFN, interferon; NIH, National Institutes of Health; PCT, porphyria cutanea tarda; SLE, systemic lupus erythematosus; SR, systematic review.

^aSources include existing systematic reviews where possible. If not available, primary sources are listed.